实时超声引导下显微手术切除脑深部病灶

目的探讨术中超声引导在脑深部病灶显微手术中的应用价值。方法自2004年开始我们在脑深部病灶显微手术中采用实时超声引导病灶定位,指引手术中皮层入路及路径的选择,并使用术中超声影像动态了解病变位置的变化情况、手术切除的范围,利用实时影像辅助判断病变切除程度。结果28例脑深部病灶,病灶直径为1.0～5.9cm,病理诊断包括蛛网膜囊肿5例,海绵状血管瘤2例,动静脉畸形2例,肿瘤7例,脑内血肿12例。所有病例均显微镜下全切,术后28例患者均恢复良好,神经功能保存良好,无新的神经功能损害,无手术并发症。结论术中超声引导是一种简便有效的脑深部病灶定位方法,操作简便,定位准确,能够实时指引手术路径和动态了解手术切除病灶的范围,与显微神经外科配合能够有效地避免额外的手术损伤,提高手术精度。     

早期乳腺导管原位癌X线表现与预后生物学标记关系的研究

目的评价乳腺导管原位癌（DCIS）及DCIS伴微浸润的X线片表现，分析X线表现与预后生物学标记的相关性。方法对50例乳腺DCIS及45例DCIS伴微浸润的患者行X线检查，共62例行预后生物学标记，分析影像表现与孕激素受体（PR）、癌基因（C—erbB-2）、抑癌基因（p53）的相关性。用卡方检验进行统计学处理，并对有意义者行优势比（OR值）分析。结果（1）单独1个X线征象表现者62例；合并2个征象26例；阴性7例。（2）各种X线征象单独分析显示，62例有钙化的病灶中恶性钙化占73％（45例），其余为中间性钙化；钙化以簇状分布最为常见（36例），其次为段样分布（18例）。22例有肿块的病灶中，以卵圆形肿块最为常见（13例）；肿块的边缘表现为浸润、小分叶、清晰和模糊各为15、1、4和2例；等密度肿块占的比例较高（55％，12例）。结构扭曲7例，除1例外多与其他征象伴行；局灶性不对称占16％（15／95），可单独发生或与其他征象伴发。（3）将病灶的X线表现分成恶性钙化、中间性钙化和非钙化3组，PR与C-erbB-2在3组中的分布有统计性意义，PR阳性表达者X线上非钙化征象发生率是中间性钙化的11．00倍[χ^2=8．571，P=0．003；95％可信区间（CI）为1．998～60．572]、恶性钙化的8．80倍（χ^2=9．748，P=0．002；95％CI为2．024～38．253）；而C—erbB-2高表达者，恶性钙化是非钙化发生的12．35倍（χ^2=7．353，P=0．007；95％CI为1．447—105．443），中间性钙化的5．74倍（χ^2=4．977，P=0．026；95％CI为1．110～29．645）。结论乳腺DCIS及DCIS伴微浸润X线征象有特征。X线征象可以作为早期乳腺DCIS的一个预后因子。     

乳腺纤维腺瘤的MRI表现及与病理对照

目的观察乳腺纤维腺瘤的多种MRI表现，分析其病理基础，从而加深对纤维腺瘤的认识，提高MRI诊断准确率。方法对33例乳腺纤维腺瘤患者（38个病灶），行常规MR平扫和动态增强检查。所有病例均经病理证实，分析比较病灶的MRI形态学、信号强度及其动态增强特点等。结果33例38个乳腺纤维腺瘤的形态学表现以分叶状、类圆形为主，占89．5％（34／38）。MRI显示内部信号多较均匀，T1WI呈等、低信号，T2WI信号多样化，高信号者的黏液样变明显（平均指数1．9），间质细胞丰富（平均指数2．2）；呈低信号者间质多硬化，间质细胞分布稀疏。不同信号强度的2种指数差异有统计学意义（x^2值分别为11．267、10．415，P值均〈0．05）。肿瘤有完整的包膜，边界多清晰者占86．8％（33／38）。增强后无或轻度强化（5／38）、明显强化（33／38）；不同强化曲线的2种指数差异无统计学意义（x^2=1．171、2．861，P〉0．05）。强化程度与患者的年龄构成有一定的相关性，年龄较轻者，强化多明显。无强化分隔者（9／33），是由于瘤体内部间质纤维组织胶原化形成。结论乳腺纤维腺瘤的MR T2WI信号及强化程度表现多样化，和其瘤体内黏液硬化程度及间质细胞含量相关。认识纤维腺瘤的特征性MRI表现有助于鉴别诊断。     

Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.     

In vivo seasonal assessment of Plasmodium falciparum sensitivity to chloroquine in two different malaria endemic communities in Southern Ghana

A two year (1992 to 1993) in vivo assessment of Plasmodium falciparum sensitivity to chloroquine was conducted in two communities at Dodowa (hyperendemic) and Prampram (mesoendemic) in Southern Ghana. A slightly modified World Helath Organization standard field test (7 day test) for response of Plasmodium falciparum asexual parasites to chloroquine was used for the survey. In 1992, 16.2% (12/74) responses were classified as exhibiting chloroquine resistance at RI (14.8% ) and RII (1.4%) in the dry season and 8.2% (10/122) responses at RI in the wet season in the hyperendemic community. Only a single response (1/144; 0.7%) at RI showed resistance in the mesoendemic community. The rest of the responses in both communities were classified as sensitive to chloroquine. In the hyperendemic community, 8.4% (13/154) of responses in the dry season showed resistance at RI and 1.3% (82/150) at RI (0.7%) and RII (0.7%) in the wet season in 1993. In the mesoendemic community 1 (1.0%) response was resistant at RI in the wet season. The rest of the responses were classified as sensitive responses to chloroquine. No RIII response was encountered in any of the communities. The pattern of RI and RII responses did not show any seasonal variations in the mesoendemic community. However, they were generally higher in the dry season than in the wet season in the hyperendemic community.     

Antioxidant enzymes and paraoxonase show a co-activity in preserving low-density lipoprotein from oxidation

Oxidative modification of low-density lipoprotein in the artery wall plays a crucial role in the development of atherosclerosis. This physiopathological mechanism is clearly inhibited by high-density lipoprotein possibly via paraoxonase enzyme activity, present in high-density lipoprotein. In this study we determined the in vitro susceptibility of low-density lipoprotein to oxidation and the effect of various factors, such as paraoxonase phenotypes, on this process. Low-density lipoprotein from healthy volunteers (n=66) was isolated using the precipitant reagent and the oxidation was evaluated by measuring the malonyl dialdehyde and diene levels. Low-density lipoprotein cholesterol and phospholipid, vitamin E, serum cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol levels, and erythrocyte antioxidant enzymes were also determined. There was no difference among the parameters with regard to gender. Low-density lipoprotein samples obtained from subjects with the AA allele were more prone to oxidation, as observed by their higher stimulated conjugated diene (P=0.041) and thiobarbituric acid-related substance (P=0.042) levels, than samples from subjects with AB or BB alleles. The subjects with the BB allele had higher superoxide dismutase (P=0.021) and catalase (insignificant increase) activities, while their conjugated diene (P=0.000) levels were lower. In conclusion, our results revealed that the high low-density lipoprotein oxidation is related to the high low-density lipoprotein cholesterol content and low phospholipid content. The present study demonstrated an increase in superoxide dismutase and catalase activities, asl well as PON1 activities, in subjects with the BB allele. Since these enzymes all show activity against low-density lipoprotein oxidation, we propose that future investigations on atherosclerotic processes should address PON1 polymorphism as well as PON1 and other antioxidant enzymes. Received: 7 May 2001 / Accepted: 14 December 2001     

High frequency of circulating gamma delta T cells with dominance of the v(delta)1 subset in a healthy population

TCR gamma delta(+) cells constitute <5% of all circulating T cells in healthy, adult Caucasians, and V(delta)1(+) cells constitute a minority of these cells. In contrast to TCR alpha beta(+) cells, their repertoire is selected extrathymically by environmental antigens. Although increased frequencies of V(delta)1(+) cells are found in several diseases, their function remains obscure. Here we show that the frequency of peripheral blood gamma delta T cells in healthy West Africans is about twice that of Caucasians, mainly due to a 5-fold increase in V(delta)1(+) cells, which is consequently the dominant subset. No age dependency of V(delta)1 frequencies was identified and the V(delta)1(+) cells in the African donors did not show preferential V(gamma) chain usage. Analysis of the CDR3 region size did not reveal any particular skewing of the V(delta)1 repertoire, although oligoclonality was more pronounced in adults compared to children. The proportions of CD8(+), CD38(+) and CD45RA(hi)CD45RO(-) cells within the V(delta)1(+) subset were higher in the African than in the European donors, without obvious differences in expression of activation markers. No significant correlations between levels of V(delta)1(+) cells and environmental antigens or immunological parameters were identified. Taken together, the evidence argues against a CDR3-restricted, antigen-driven expansion of V(delta)1(+) cells in the African study population. Our study shows that high frequencies of TCR gamma delta(+) cells with dominance of the V(delta)1(+) subset can occur at the population level in healthy people, raising questions about the physiological role of V(delta)1(+) T cells in the function and regulation of the immune system.